We did run two fairly large lists for customers, over 80,000 people on each list.
The fact is that mailscanner cannot handle the load and creates a backlog to mailman which then chokes. We tried to finetune things with the help of the mailman team but it simple would not work. When we took mailscanner out and replaced it by exiscan things did run smoothly. On top the new VERP bounce probes mailman uses will overload mailscanner easily on a large list because they are single messages.
The only way that comes to mind would be using split spool directories in exim and mailscanner but that is rather tricky to set up.
Exiscan is so much easier and works right at the smtp server and not has to pick up and drop off message files (two disk i/o's additional per message!).

I can see that being a problem. I have been starting to see very busy servers having issues with the dual mail queue setup with MailScanner. One of the biggest issues I see with these very busy servers is the fact that MailScanner runs before the Exim filtering is done. This means that it will scan email that ultimately is :blackhole:'d which is pretty silly. I don't believe, ultimately, that it's a MailScanner issue per se, more a limitation of the combination of the two - Exim and MailScanner. On servers I've have running sendmail with MailScanner, I've not seen such issues.